The pitfall of all chemotherapeutics lies in drug resistance and the severe side effects experienced by patients. One way to reduce the off-target effects of chemotherapy on healthy tissues is to alter the biodistribution of drug. This can be achieved in two ways: Passive targeting utilizes shape, size, and surface chemistry to increase particle circulation and tumor accumulation. Active targeting employs either chemical moieties (e.g. peptides, sugars, aptamers, antibodies) to selectively bind to cell membranes or responsive elements (e.g. ultrasound, magnetism, light) to deliver its cargo within a local region. This article will focus on the systemic administration of anti-cancer agents and their ability to home to tumors and, if relevant, distant metastatic sites.